Cleveland Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Genes (Basel). 2022 Dec 30;14(1):111. doi: 10.3390/genes14010111.
Glaucoma is the leading cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG), the most common glaucoma subtype, is more prevalent and severe in individuals of African ancestry. Unfortunately, this ancestral group has been historically under-represented among genetic studies of POAG. Moreover, both genetic and polygenic risk scores (GRS, PRS) that are typically based on genetic data from European-descent populations are not transferable to individuals without a majority of European ancestry. Given the aspirations of leveraging genetic information for precision medicine, GRS and PRS demonstrate clinical potential but fall short, in part due to the lack of diversity in these studies. Prioritizing diversity in the discovery of risk variants will improve the performance and utility of GRS and PRS-derived risk estimation for disease stratification, which could bring about earlier POAG intervention and treatment for a disease that often goes undetected until significant damage has occurred.
青光眼是全球导致不可逆性失明的主要原因。原发性开角型青光眼（POAG）是最常见的青光眼亚型，在非洲裔人群中更为普遍和严重。不幸的是，在 POAG 的遗传研究中，这个祖先群体在历史上一直代表性不足。此外，通常基于欧洲血统人群遗传数据的遗传和多基因风险评分（GRS、PRS）不能转移到没有多数欧洲血统的个体。鉴于利用遗传信息进行精准医学的愿望，GRS 和 PRS 具有临床潜力，但存在不足，部分原因是这些研究缺乏多样性。在发现风险变异体时优先考虑多样性，将提高 GRS 和 PRS 衍生的风险估计在疾病分层中的性能和实用性，这可能会带来更早的 POAG 干预和治疗，因为这种疾病常常在发生严重损害之前未被发现。
